Hydroxy-ethoxy derivatives of



Patented Nov. 29, 1938 UNITED STATES HYDROXY-ETHOXY DERIVATIVES, or 2- PHENYLQUINOLINEJLCARBOXYLIG ACID ANDMETHOD or MAKING'SAME Paul Diedrich, Finkenkrug, Germany, assignor to Shering-Kahlbaum A. G., Berlin, Germany, a corporation of Germany No Drawing. Original application February 20,

1934, Serial No. 712,254. Divided and this application March 4, 1936, Serial No. 67,089. In Germany February 22, 1933 Claims.

This invention relates to derivatives of 2- phenyl-quinolin-4-carboxylic acid and more particularly to hydroxy-alkyl hydroxy derivatives of the latter and methods of making same.

This application is a division of my copending application Ser. No. 712,254, filed February 20, 1934, entitled I-Iydroxy alkoxy derivatives of 2-phenylquinoline-4-carboxy1ic acid and method of making same, now Patent No. 2,064,297, dated December 15, 1936.

Hydroxy compounds of the Z-phenylquinoline- 4-carboxylic acid are already known. The comparative pharmacological investigation of these compounds, however, shows that they possess the same toxicity to animals as the 2-phenylquinoline--carboxylic acid itself. The same applies to the alklated hydroxy compounds of said acid which do not differ in this respect from the nonalkylated hydroxy compounds nor from the 2- phenylquinoline-4-carboxylic acid.

One object of this invention is to provide derivatives of hydroxy-Z-phenylquinoline-4-carboxylic acids which show considerably less toxicity than the hydroxy acids themselves but about the same therapeutical efiiciency. It has been found that the hydroxyalkylated derivatives of said hydroxy 2 phenylquinoline 4 carb-oxylic acids possess these valuable properties.

Another object of this invention consists in producing said hydroxyalkylated hydroxy derivatives of said phenylquinoline-4-carboxylic acid. For this purpose hydroxyalkyl hydroxyanilines are reacted with benzaldehyde and pyroracemic acid.

The following are specific examples of the practice of the present invention:

EXAMPLE 1 2-phenyZ-6-hydroxyethomy quinolz'ne-el-carboxylic acid 24 grams of the hydroxyethylether of p-aminophenol are boiled in 150 cos. of alcohol with 16 grams of benzaldehyde for 30 minutes wherefrom a small amount of alcohol. The acid obtained forms an amorphous, light-brown, tasteless powder of the melting point 198 C.

EXAMPLE 2 crystallization from dilute alcohol a yellow crystal powder of the melting point of 190 C.

While I have described the present invention setting forth two specific embodiments thereof, it is to be understood that my invention is not limited thereto, but that the invention includes other specific compounds and the manufacture thereof. My invention is, therefore, not to be limited except by the claims appended hereto.

What 1' claim as my invention is:

1. Z-phenyl-S-hydroxyethoxy quinoline-l-carboxylic acid, exhibiting considerably less toxicity than the hydroxy-Z-phenyl quinoliniE-L-carboxylic acids, but being of about the same therapeutical value as the latter, and representing an amorphous, light-brown tasteless powder.

2. 2-phenyl-8-hydroxyethoxy quinolinel-carboxylic acid, exhibiting considerably less toxicity than the hydroxy-Z-phenyl quinolinel-carboxylic acids, but being of about the same therapeutical value as the latter, and representing a yellow crystalline material.

3. A Z-phenyl hydroxyethoxy-quinoline-l-carboxylic acid selected from the group consisting of 2-phenyl-(i-hydroxyethoxy-quinoline 4 carboxylic acids and 2-phenyl-8-hydroxyethoxyquinoline-4carboxylic acids, said acid exhibiting considerably less toxicity than the hydroxy-2- phenyl-quinoline-4-carboxylic acids.

4. A method of producing hydroxy alkoxy derivatives of Z-phenyl quinolinel-carboxylic acid which comprises heating a compound taken from the group consisting of the oand p-hydroxy alkoxy anilines with benzaldehyde and pyroracemic acid and isolating the reaction product.

5. A method of producing hydroxy alkoxy derivatives of 2-phenyl quinoline-4-carboxylic acid,

which comprises heating a compound taken from the group consisting of the oand p-hydroxy-ethyl ethers of an amino phenol with benzaldehyde and pyroracemic acid and isolating the reaction product.

6. A method of producing hydroxy alkoxy derivatives of Z-phenyl quinoline-l-carboxylic acid which comprises slowly adding pyroracemic acid to a boiling solution of a compound taken from the group consisting of the oand p-hydroxy alkoxy-anilines and benzaldehyde, and isolating the reaction product.

7. A method of producing hydroxy alkoxy derivatives of 2-phenyl quinoline--carboxylic acid which comprises slowly adding pyroracemic acid to a boiling solution of a compound taken from the group consisting of the oand p-hydroxy alkoxy anilines and benzaldehyde in alcohol and isolating the reaction product.

8. A method of producing hydroxy alkoxy derivatives of 2-pheny1 quinolinel-carboxylic acid, which comprises slowly adding pyroracemic acid to a boiling solution of a compound taken from the group consisting of the 0- and p-hydroxy alkoxy anilines and benzaldehyde in alcohol, continuing the boiling for several hours, distilling off the alcohol and isolating and purifying the reaction product.

9. A method of producing hydroxy alkoxy derivatives of 2-phenyl quinoline-l-carboxylic acid, which comprises slowly adding pyroracemicacid to a boiling solution of a compound taken from the group consisting of the 0- and p-hydroxy alkoxy anilines and benzaldehyde in alcohol, continuing the boiling for several hours, distilling off the alcohol, extracting the residue with aqueous sodium carbonate solution, acidifying the extract obtained and purifying the precipitate.

10. A method of producing hydroxy alkoxy derivatives of Z-phenyl quinoline-l-carboxylic acid, which comprises slowly adding pyroracemio acid to a boiling solution of a compound taken from the group consisting of the oand p-hydroxy alkoxy anilines and benzaldehyde in alcohol, continuing the boiling for several hours, distilling oi the alcohol, extracting the residue with aqueous sodium carbonate solution, acidifying the extract obtained, isolating the precipitate and recrystallizing the latter from aqueous alcohol.

PAUL DIEDRICH. 

